A predominant serotype of human immunodeficiency virus type-1 (HIV-1) exists in Europe and the United States based on molecular seroepidemiologic analysis of the V3 region of the envelope gpl2O. This hypervariable region behaves immunologically as a linear epitope when synthesized and used as an immunogen in laboratory animals. The hypervariability of the primary amino acids in this region was thought to convey the type-specificity observed previously for neutralizing antibody made to this request. Experimental studies done this past year have now demonstrated this region to be part of a conformational epitope as evidenced by the virus' ability to escape a V3-specific MoAb without changing an), of the primary amino acids in the antibody binding site. Neutralizing antibody subsequently directed at the V3 region following infection is correlated in the selection of escape mutants. The virus has two mechanisms for evading the humoral system and will require vaccines to consider this in their subsequent design. Viruses passaged in vitro in primary lymphocyte cell lines select the most replication-competent virus subpopulations. Escape mutants arise from the less-replication competent subpopulations. Mechanisms are operating in addition to a strong humoral response(s) in HIV-1 infected chimpanzees to restrict and possibly control the virus in this species. This model appears to be very instructive for efficacy immunogenicity testing and challenge for examining the sterilizing immunity of a prototype HIV-1 vaccine. The use of the model for disease prevention is in serious doubt.